Liquid drop dispensers of the type to which the present invention pertains are available in various sizes and shapes and act by various mechanisms for dispensing of the liquid contents. One problem associated with conventional dispensers was the difficulty in accurately controlling the amount of medicine dispensed, i.e., the number of drops and the volume of the drop to be dispensed. There is a need for dispensing microliter amounts of a liquid in the form of a drop, especially during the administration of medicaments to a body cavity. This is because if the drop volume is not controlled, excess medicament administered may lead to the risk of systemic toxicity by the medicament and also cause a waste of medicaments. This is particularly relevant for ocular medicaments wherein the systemic toxicity is, in part, a function of the relatively large size of the commercial eyedrops.
The average size of a conventional ophthalmic eyedrop is approximately 50 to 70 microliter. However, the tear film normally contains only 7 to 10 microliter. If an eyedrop is instilled, the tear film can momentarily hold as much as 30 microliter before the subject blinks. The remainder of the eyedrop, at least 20 to 40 microliter, spills out onto the cheek. Rapid blinking quickly restores the normal tear volume by pumping the excess into the nasolacrimal system. It is estimated that 80% of an eyedrop drains via this route, where it can be systemically absorbed. With larger eyedrops, more medicament passes into the nasolacrimal sac, increasing absorption and the risk of toxicity (Brown, R H et al., Am J Ophthal., 99, April 1985, 460-464). From a biopharmaceutical and toxicological point of view, it has been suggested that the decrease in drop size to between 5 to 15 microliter would reduce the rate of medicament loss through drainage, the incidence of systemic toxic effects, and, in addition, the cost of therapy (Sklubalova Z et al., DDIP, 32, 2006, 197-205). Brown, R H et al tested a bottle having a delivery orifice tip. They varied the internal and outer diameter of the tip and found that for fixed internal diameters in the range from about 0.02 inches to about 0.06 inches, increase in outer diameter from about 0.02 inches to about 0.18 inches resulted in an increase in drop size from about 10 microliter to about 60 microliter. An eyedrop of less than 25 microliter was always delivered when the outer diameter of the tip was less than 0.047 inches. Brown, R H et al further discloses that the bottle has two chambers, an inner chamber containing the liquid and an outer chamber that ends in the delivery orifice tip on one end and a second narrow aperture on the other end separating the outer chamber from the inner chamber. When the bottle is squeezed, the liquid emerges as a drop rather than a stream.
U.S. Pat. No. 5,356,052 relates to drop dispenser for accurate dispensing of drops of a predetermined size. The dispenser has a neck that has a flat flow passage or an orifice leading to a chamber, the chamber ending in a delivery aperture. The liquid from the container is forced into a flat flow passage in the neck and discharged into a chamber in the tip where the liquid coalesces. The liquid is then dispensed through an aperture whose dimensions determine the size of the drop dispensed.
U.S. Pat. No. 5,673,822 relates to a device for the dropwise delivery of a fluid contained in a flexible vial, the device comprising a tubular casing capable of surrounding the vial, wherein the casing is provided with a bottom portion whose inner surface lies opposite the outer surface of the bottom wall of the vial, and the bottom portion of the casing is equipped with a resiliently displaceable tab which can be moved so as to press against the bottom wall of the vial in order to squeeze the vial and drive out a drop of fluid. It is disclosed that the stroke of the tab is ideally determined such that only one drop is expelled. In order to enable that the vial be squeezed, the whole bottle is made flexible. As the bottle itself should maintain its rigidity, this flexibility is limited. The tab presses on a flat wall and we find that generally volume displaced may be large because a full wall on the bottle rather than a fixed portion of the wall is depressed.